Achieving high efficiency has been a constant goal in organic synthesis. Tandem reactions, which combine two or more bond forming reactions into a single synthetic operation and eliminate the necessity of separation/purification of reaction intermediates, can concomitantly generate multiple bonds with a rapid increase in molecular complexity and could form carbon frameworks that are difficult to access by other methods. Tandem reactions intrinsically possess high synthetic efficiency for organic synthesis. Although organodiboronic acids/acid esters are readily available, their application in transition metal-catalyzed addition reactions remains unexplored. The development of new tandem reactions with organodiboronic acids/acid esters as nucleophiles, which could lead to ring systems that are difficult to obtain by existing methods and could significantly simplify the preparation of biologically important compounds, is fundamentally significant and synthetically useful. In this application, the development of Type I palladacycle-catalyzed tandem double addition reactions with organodiboronic acid esters as nucleophiles, including asymmetric versions, for organic synthesis is described. New tandem double addition reactions of 1,2-arenediboronic acid esters and 1,2-ethenediboronic acid esters with 1,2-unsaturated carbonyl-containing compounds, 1,n-alkanedials and divinyl ketones will be investigated. The development of highly stereoselective Type I palladacycles for the asymmetric tandem double addition reactions will also be carried out. In addition, the synthetic application of these new Type I palladacycle-catalyzed tandem double additions for the synthesis of two biologically important compounds, Indatraline and Englerin A, will be investigated. The long term goal of the proposed research is to develop new highly efficient tools/processes for the synthesis of biologically important compounds. The successful accomplishment of the proposed research is expected to open a new avenue for addition reactions with organodiboronic acid esters as nucleophiles and to pave the road for the development of other new tandem reactions for organic synthesis. The proposed research is also expected to have great impact on the synthesis and study of many biologically important compounds. The interdisciplinary nature of the proposed study makes it an excellent vehicle for training participants including undergraduate students, graduate students and postdoctoral associates. PUBLIC HEALTH RELEVANCE: New Type I palladacycle-catalyzed tandem double addition reactions of organodiboronic acid esters with carbonyl-containing compounds will be investigated. This research is expected to provide the synthetic community highly efficient tools for the synthesis of biologically important compounds (drugs).